Cartilage is a primary or secondary target organ for many skeletal and joint disorders. In some congenital disorders (cartilage dysplasias), cartilage growth is inherently abnormal. In some arthritides (osteoarthritis), defective chondrocyte metabolism may be primarily deranged. In other arthritides (rheumatoid arthritis), cartilage is secondarily attached by the underlying disease process and clinical join dysfunction results from failure of cartilage repair. In some conditions such as acromegaly, uncontrolled growth of cartilage leads to arthritis. These diverse clinical disorders document a need to understand the basic factors which control cartilage growth and repair. My efforts are designed to investigate the role of hormones and metabolic factors that directly affect cartilage growth and by what mechanisms these effects can be produced. I had identified several hormones that stimulate cartilage growth in vitro. The increase in growth is not mediated by the same mechanisms. For example, cyclic AMP causes growth primarily through cellular hyperplasia of immature chondrocytes; whereas thyroid hormones stimulate cartilage hypertrophy and cartilage maturation. I plan to extend these studies by addressing the following questions: What are the mechanisms by which thyroid hormones stimulate growth? 2) Will increasing local concentrations of cyclic AMP promote growth of mammalian growth-plate and non-growth-plate cartilage? 3) Is alkaline phosphatase, a marker of cartilage maturation, involved as a regulatory of membrane phosphorylation? Organ culture of embryonic chick pelvic cartilage and the growth-plate cartilage from the fetal pig scapula offers useful models to address these questions. Cartilages are aseptically removed, randomly distributed into serum-free medium, hormone added, and the cartilages incubated for 3 to 14 days. Estimates of the rates of collagen, proteoglycan, and DNA synthesis are determined by incorporation of radiolabeled precursors. Wet and dry cartilage weight, cartilage length, DNA content, glycosaminoglycan content, alkaline phosphatase activity, and total soluble protein are measured. Histologic, autoradiographic, and ultrastructural features help characterize the hormonal effects on cartilage growth. These studies are fundamental to the understanding of the hormonal control of cartilage growth and metabolism and may provide new insights into therapies leading to cartilage repair.